The major objective of the proposed research is to study the chemical and physical properties of selenenic acids and their derivatives. The selenium in the mammalian enzyme glutathione peroxidase (GSH-Px) is believed to be present at the oxidation state of a selenenic acid. A number of important reactions of organoselenium compounds (electrophilic additions to olefins, selenoxide syn eliminations and (2,3)sigmatropic rearrangements) are thought be have selenenic acid derivatives as intermediates. A variety of selenenic acids will be generated at low temperature by syn elimination of appropriate selenoxides. The decomposition products will be spectroscopically monitored (IR,NMR) to determine whether selenenic acids are being formed, what their lifetime is, and what disproportionation intermediates and products can be detected. The effects of sterically hindering, electron withdrawing, and hydrogen bonding substituents on the reactions of selenenic acids and on their lifetime will be examined. If stable selenenic acids can be synthesized, their activity as catalysts for the oxidation of thiols by alkyl hydroperoxides (a probable metabolic role for GSH-Px) will be studied. Their reactions with olefins will be studied to determine whether a suitably constructed olefin analog of glutathione might not serve as a specific inhibitor of GSH-Px. The chemistry of several selenenic acid derivatives (ester, amides, anhydrides) will also be studied. The selenium-77 NMR chemical shifts of representative stable seleneic acid derivatives will be determined to aid in identifying this functional group in situations where the selenenic acid can be observed but not isolated. Finally, the applicability of selenenic acid chemistry to organic synthesis will be examined.